Hairy cell leukemia in association with thrombotic thrombocytopenic purpura and factor VIII antibodies.

A unique patient is reported with longstanding hairy cell leukemia who manifested two distinct abnormalities of factor VIII; factor VIII antibodies and recurrent thrombotic thrombocytopenic purpura (TTP). The patient presented in 1977 with splenomegaly and pancytopenia and was diagnosed with hairy cell leukemia and was treated with splenectomy. In 1989 he received interferon-alpha because of a relapse which resulted in a hematologic remission. Hospitalization on two occasions for gross hematuria was caused by the development of a factor VIII antibody. He was successfully treated on both occasions with cyclophosphamide, prednisone and active prothrombin complex (FEIBA). In October 1991 he presented with microangiopathic hemolytic anemia and thrombocytopenia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made. Repeat bone marrow biopsy showed hairy cell leukemia. The patient responded to treatment with plasmapheresis, fresh frozen plasma replacement and prednisone. He had two subsequent relapses with the last being refractory and subsequently fatal. During the initial manifestation of TTP and in follow-up evaluation unusually large von Willebrand factor multimers were demonstrated.

Involvement of mast cells by the malignant process in patients with Philadelphia chromosome negative myeloproliferative neoplasms.

The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies frequently characterized by a mutation in JAK2 (JAK2V617F). Peripheral blood (PB) CD34(+) cells from patients with polycythemia vera (PV) and primary myelofibrosis (PMF) generated in vitro significantly fewer mast cells (MCs) than normal PB CD34(+) cells. The numbers of MC progenitors assayed from MPN CD34(+) cells were, however, similar to that assayed from normal CD34(+) cells. A higher percentage of the cultured MPN MCs expressed FcvarepsilonRIalpha, CD63 and CD69 than normal MCs, suggesting that cultured MPN MCs are associated with an increased state of MC activation. Further analysis showed that a higher proportion of cultured PV and PMF MCs underwent apoptosis in vitro. By using JAK2V617F, MplW515L and chromosomal abnormalities as clonality markers, we showed that the malignant process involved MPN MCs. JAK2V617F-positive MC colonies were assayable from the PB CD34(+) cells of each of the 17 JAK2V617F positive MPN patients studied. Furthermore, erlotinib, a JAK2 inhibitor, was able to inhibit JAK2V617F-positive PV MC progenitor cells, indicating that malignant MC progenitor cells are a potential cellular target for such JAK2 inhibitor-directed therapy.

Spurious fibrinogen levels secondary to pyroglobulinemia in Waldenström's macroglobulinemia.

We report two cases of pyroglobulinemia detected in the course of routine determination of fibrinogen levels measured by the heat-precipitation method and that led to the diagnosis of Waldenström's macroglobulinemia. The incidence of pyroglobulinemia is briefly discussed, and the potential significance of this laboratory artifact is emphasized.

Pneumatosis cystoides intestinalis: a complication of systemic chemotherapy.

A case of pneumatosis cystoides intestinalis following administration of chemotherapy for Hodgkin's disease is presented. Because of a poor response to nonoperative management, a subtotal colectomy was performed. Although the pathogenesis of pneumatosis cystoides intestinalis is not entirely clear, it seems likely that, in this case, mucosal ulceration secondary to methyl-gag allowed intraluminal air to dissect into the intestinal wall and surrounding retroperitoneal tissues. Because pneumatosis cystoides intestinalis is often reversible and self-limited, fecal diversion in lieu of bowel resection is entertained as a possible alternative in the operative management of selected cases. In the case presented resection was performed because of extent of the pathologic process.

Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation?

Different hematologic abnormalities are often encountered in patients with inflammatory bowel disease. Among them anemia, leukocytosis, and thrombocytosis are commonly seen. Leukopenia and thrombocytopenia are observed mostly as a side effect of therapy, particularly with use of immunosuppressive drugs. Immune thrombocytopenic purpura is rarely reported in association with inflammatory bowel disease. We present two cases with combination of these entities along with a literature review and treatment options. Immune thrombocytopenic purpura in these patients presented as an extraintestinal manifestation of inflammatory bowel disease mediated by a disturbance of the immune system.

Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study.

To test the effectiveness of 6-mercaptopurine (6-MP) in the treatment of Crohn's disease, we entered 83 chronically ill patients into a two-year double-blind study comparing 6-MP with placebo. Crossover data showed that improvement occurred in 26 of 39 courses of 6-MP (67%) as compared with three of 39 courses of placebo (8%) (P less than 0.001). Non-crossover data likewise confirmed the superiority of 6-MP. The drug was more effective than placebo in closing fistulas (31 vs 6%) and in permitting discontinuation or reduction of steroid dosage (75 vs. 36%) (P less than 0.001). The onset of response to 6-MP was often delayed, with 32% of patients taking longer than three months to respond, and 19% taking longer than four months. Adverse side effects to 6-MP occurred in 10% of patients and were uniformly reversible. We conclude that 6-MP is an effective and useful agent in the management of Crohn's disease.

Malignant neoplasms subsequent to treatment of inflammatory bowel disease with 6-mercaptopurine.

OBJECTIVE: Most complications of 6-mercaptopurine (6MP) used in the treatment of inflammatory bowel disease (IBD) occur early, whereas neoplasms occur late in the course. Concern persists that the risk is increased when 6MP is used. We report our experience with malignant tumors developing over 27 yr of treating IBD patients with 6MP. METHODS: A total of 591 patients with IBD treated with 6MP between 1969 and 1997 were followed or traced until present to identify all malignant tumors and blood dyscrasias that had developed to determine the type, distribution, and duration of the IBD, the dose and duration of 6MP therapy, the concurrent versus previous use of 6MP, the incidence and probable relationship of 6MP to specific neoplasms, and whether the 6MP had been effective in treatment. RESULTS: A total of 550 patients (93%) fulfilled the criteria for follow-up; these included 380 with Crohn's disease (CD) and 170 with ulcerative colitis (UC). Twenty-five patients had developed neoplasms (16 of 380 CD and nine of 170 UC) (p = 0.66). In half of the cases, the goal of therapy had been achieved with 6MP. In 10 patients, the neoplasm was diagnosed while the patients were taking 6MP (40%) and in 15, many years after the 6MP had been terminated (60%). The incidence of neoplasms (25 of 550) was 2.7/1000 patient-years of follow-up. The most common neoplasms were found in the bowel (eight of 550, 1.6%; five CD, and three UC), and breast (three, 0.5%; two CD, and one UC). Non-Hodgkins lymphomas occurred in two patients with CD; one was cerebral and the other abdominal. One patient with CD developed leukemia. The duration of 6MP therapy ranged from 5 months to 22 yr, with a mean of 5 yr. The dose of 6MP ranged from a quarter of a tablet/day (12.5 mg) to 100 mg/day, with the majority in a range from 50 to 75 mg/day. CONCLUSION: In no instance could a neoplasm be attributed to the use of 6MP. The incidence of colon cancer is not greater than that with long standing colitis. Suspicion of a relationship between 6MP and leukemia/lymphoma persists, but the incidence is low. This must be weighed against the improved quality of life due to 6MP for patients with IBD.

Multicentric angiofollicular lymph node hyperplasia with peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis in women. A distinct syndrome.

Four women with multicentric angiofollicular lymph node hyperplasia had a distinct clinical syndrome characterized by peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis. The nodes displayed typical morphologic changes of the plasma cell variant of multicentric angiofollicular lymph node hyperplasia. The pathologic changes are morphologically distinct from angioimmunoblastic lymphadenopathy with dysproteinemia although clinical similarities do exist. In these four cases, the lymphadenopathy was usually bulky and multicentric. There was frequent splenic involvement. The neuropathies were severe and disabling. Clinical courses have been variable with some responses to therapy with steroids and alkylating agents. No neoplastic transformations have occurred. Multicentric angiofollicular lymph node hyperplasia may represent a reactive lesion in which the antigenic stimulus is unknown but results in follicular hyperplasia, angiogenesis, and the systemic manifestations of hyperimmune stimulation. We believe this clinical syndrome may represent a distinct variant of multicentric angiofollicular lymph node hyperplasia, and it requires close observation for neoplastic transformation and other complications of its multisystem nature.

Chemotherapy of metastatic Merkel cell cancer.

Out of 16 cases of Merkel cell cancer identified in the records of the Mt. Sinai Medical Center or affiliates, 11 patients developed systemic metastases. Literature review confirms the substantial possibility of dissemination. Both in our series and in the literature, cytotoxic chemotherapy produced a high rate of usually short-lived response, although one of our patients with disseminated metastases achieved complete remission for two years.